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0 °C

2,2,6,6-Tetramethylpiperidine-1-oxyl radical (0.05 mg, 0.3 μmol) was added at room temperature to a suspension of (3S,5S)-5-hydroxymethyl-3-methyl-4-oxo-octahydro-9-oxa-2,4a-diaza-benzocycloheptene-2-carboxylic acid benzyl ester (example 23B, 102 mg, 0.29 mmol) and trichloroisocyanuric acid (72 mg, 0.29 mmol) in DCM (1 mL), then after 5 min the mixture was washed with 1 M aq. sodium sulfite solution and brine. The organic layer was dried over magnesium sulfate, filtered, and evaporated. The residue [(3S,5S)-5-oxomethyl-3-methyl-4-oxo-octahydro-9-oxa-2,4a-diaza-benzocycloheptene-2-carboxylic acid benzyl ester] was dissolved in DCM (1 mL) and added dropwise at room temperature to a suspension of (S)-6-aza-spiro[2.5]octan-4-ol hydrochloride (48 mg, 0.29 mmol), Et3N (30 mg, 0.29 mmol), HOAc (35 mg, 0.58 mmol) and sodium triacetoxyborohydride (70 mg, 0.32 mmol) in DCM, then after 16 h the reaction mixture was cooled to 0° C. and partitioned between EtOAc and 1 M aq. sodium carbonate solution. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; DCM→DCM/MeOH/25% aq. ammonia solution 90:10:0.25) produced the title compound (70 mg, 52%). Light yellow gum, MS: 458.4 (M+H)+.

1. washafter 5 min the mixture was washed with 1 M aq. sodium sulfite solution and brine
2. dry with materialThe organic layer was dried over magnesium sulfate
3. filtrationfiltered
4. customevaporated
5. dissolutionThe residue [(3S,5S)-5-oxomethyl-3-methyl-4-oxo-octahydro-9-oxa-2,4a-diaza-benzocycloheptene-2-carboxylic acid benzyl ester] was dissolved in DCM (1 mL)
6. custompartitioned between EtOAc and 1 M aq. sodium carbonate solution
7. washThe organic layer was washed with brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. customevaporated